Abstract
The mothering ability of a sow largely depends on the shape and function of the mammary gland. The aim of this study was to identify QTL for the heritable inverted teat defect, a condition characterized by disturbed development of functional teats. A QTL analysis was conducted in a porcine experimental population based on Duroc and Berlin Miniature pigs (DUMI). The significant QTL were confirmed by linkage analysis in commercial pigs according to the affected sib pair design and refined by family-based association test (FBAT). Nonparametric linkage (NPL) analysis revealed five significant and seven suggestive QTL for the inverted teat defect in the porcine experimental population. In commercial dam lines five significant NPL values were detected. QTL regions in overlapping marker intervals or close proximity in both populations were found on SSC3, SSC4, SSC6, and SSC11. SSC6 revealed QTL in both populations at different positions, indicating the segregation of at least two QTL. The results confirm the previously proposed polygenic inheritance of the inverted teat defect and, for the first time, point to genomic regions harboring relevant genes. The investigation revealed variation of the importance of QTL in the various populations due to either differences in allele frequencies and statistical power or differences in the genetic background that modulates the impact of the liability loci on the expression of the disease. The QTL study enabled us to name a number of plausible positional candidate genes. The correspondence of QTL regions for the inverted teat defect and previously mapped QTL for teat number are in line with the etiologic relationship of these traits.
Similar content being viewed by others
References
Beeckmann P, Moser G, Bartenschlager H, Reiner G, Geldermann H (2003a) Linkage and QTL mapping for Sus scrofa chromosome 8. J Anim Breed Genet 120:66–73
Beeckmann P, Schroffel J, Moser G, Bartenschlager H, Reiner G, et al. (2003b) Linkage and QTL mapping for Sus scrofa chromosome 1. J Anim Breed Genet 120:1–10
Bhattacharjee M, Vonderhaar BK (1984) Thyroid-hormones enhance the synthesis and secretion of alpha-lactalbumin by mouse mammary tissue in vitro. Endocrinology 115:1070–1077
Bignell G, Micklem G, Stratton MR, Ashworth A, Wooster R (1997) The BRC repeats are conserved in mammalian BRCA2 proteins. Hum Mol Genet 6:53–58
Bohmer FD, Kraft R, Otto A, Wernstedt C, Hellman U, et al. (1987) Identification of a polypeptide growth inhibitor from bovine mammary-gland – sequence homology to fatty acid-binding and retinoid-binding proteins. J Biol Chem 262:15137–15143
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: Actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268
Brevern N, Schimpf B, Wörner R, Swalve H (1994) Parameterschätzung für Zitzenmerkmale bei Hybridsauen. Züchtungskunde 66:339–348
Cassady JP, Johnson RK, Pomp D, Rohrer GA, Van Vleck LD, et al. (2001) Identification of quantitative trait loci affecting reproduction in pigs. J Anim Sci 79:623–633
Cepica S, Reiner G, Bartenschlager H, Moser G, Geldermann H (2003) Linkage and QTL mapping for Sus scrofa chromosome X. J Anim Breed Genet 120:144–151
Chomdej S (2005) Molecular genetic analysis of positional candidate genes for mammary gland characteristics in pigs. Thesis, Rheinische Friedrich-Wilhelms–Universität, Bonn
Chomdej S, Ponsuksili S, Schellander K, Wimmers K (2004) Sequencing, SNP identification and mapping of the porcine PTHLH gene to chromosome 5. Anim Genet 35:151–152
Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138:963–971
Clayton GA, Powell JC, Hiley PG (1981) Inheritance of teat number and teat inversion in pigs. Anim Prod 33:299–304
Dragos-Wendrich M, Moser G, Bartenschlager H, Reiner G, Geldermann H (2003) Linkage and QTL mapping for Sus scrofa chromosome 10. J Anim Breed Genet 120:82–88
Dunbar ME, Dann P, Brown CW, Van Houton J, Dreyer B, et al. (2001) Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes. J Endocrinol 171:403–416
Dundar B, Dundar N, Erci T, Bober E, Büyükgebiz A (2005) Leptin levels in boys with pubertal gynecomastia. J Pediatr Endocrinol Metab 18:929–934
Geldermann H, Muller E, Moser G, Reiner G, Bartenschlager H, et al. (2003) Genome-wide linkage and QTL mapping in porcine F-2 families generated from Pietrain, Meishan and Wild Boar crosses. J Anim Breed Genet 120:363–393
Green P (1992) Construction and comparison of chromosome-21 radiation hybrid and linkage maps using Cri-Map. Cytogenet Cell Genet 59:122–124
Große Beilage E, Steffens S, Schoon HA, Bollwahn W (1996) Zitzenkörperhypoplasien und -aplasien (Stülpzitzen) bei weiblichen und männlichen Schweinen. Tierärztl Praxis 24:31–35
Günther C (1984) Morphologie der sogenannten “Stülpzitze” beim Schwein im Vergleich zum histologischen Bild einer normalen Zitze. Thesis, Freie Universität, Berlin
Haley CS, Lee GJ, Richie M (1995) Comparative reproductive performance in Meishan and Large White pigs and their crosses. Anim Sci 60:259–267
Hirooka H, de Koning DJ, Harlizius B, van Arendonk JAM, Rattink AP, et al. (2001) A whole-genome scan for quantitative trait loci affecting teat number in pigs. J Anim Sci 79:2320–2326
Horvath S, Xu X, Lake SL, Weiss ST, Silverman EK, et al. (2003) Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics. Am J Hum Genet 73:610–610
Hovey RC, Harris J, Hadsell DL, Lee AV, Ormandy CJ, et al. (2003) Local insulin-like growth factor-II mediates prolactin-induced mammary gland development. Mol Endocrinol 17:460–471
Hu Z, Reecy JM (2007) Animal QTLdb: beyond a repository A public platform for QTL comparisons and integration with diverse types of structural genomic information. Mamm Genome 18:1–4
Hu Z, Dracheva S, Jang W, Maglott D, Bastiaansen J, et al. (2005) A QTL resource and comparison tool for pigs: PigQTLDB. Mamm Genome 16:792–800
King AH, Jiang ZH, Gibson JP, Haley CS, Archibald AL (2003) Mapping quantitative trait loci affecting female reproductive traits on porcine chromosome 8. Biol Reprod 68:2172–2179
Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996) Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 58:1347–1363
Lander E, Kruglyak L (1995) Genetic dissection of complex traits – guidelines for interpreting and reporting linkage results. Nat Genet 11:241–247
Lee SS, Chen Y, Moran C, Cepica S, Reiner G, et al. (2003a) Linkage and QTL mapping for Sus scrofa chromosome 2. J Anim Breed Genet 120:11–19
Lee SS, Chen Y, Moran C, Stratil A, Reiner G, et al. (2003b) Linkage and QTL mapping for Sus scrofa chromosome 5. J Anim Breed Genet 120:38–44
Ling C, Svensson L, Oden B, Weijdegard B, Eden B, et al. (2003) Identification of functional prolactin (PRL) receptor gene expression: PRL inhibits lipoprotein lipase activity in human white adipose tissue. J Clin Endocrinol Metab 88:1804–1808
Mayer JPF (1995) Gesäugeasymmetrie und Stülpzitzenbefall bei Jungsauen. Arch Tierz Dummerstorf 38:97–91
Mayer J, Pirchner F (1995) Asymmetry and inverted nipples in gilts. Arch Tierz Dummerstorf 38:87–91
McNeilly S (1994) Suckling and the control of gonadotropin secretion. In: Knobil E, Neill JD (eds) The Physiology of Reproduction. vol 2, Chap. 60, Raven Press, New York, pp 1179–1212
Meyers SN, Rogatcheva MB, Larkin DM, Yerle M, Milan D, et al. (2005) Piggy-BACing the human genome – II. A high-resolution, physically anchored, comparative map of the porcine autosomes. Genomics 86:739–752
Musilova P, Kubickova S, Vozdova M, Rubes J (2000) Mapping of the oncogene c-myc (MYC) and the breast cancer susceptibility gene (BRCA2) in the pig by FISH. Anim Genet 31:154–154
Nordby JE (1934) Congenital defects in the mammae of swine. J Hered 25:499–502
Plath A, Einspanier R, Peters F, Sinowatz F, Schams D (1997) Expression of transforming growth factors alpha and beta-1 messenger RNA in the bovine mammary gland during different stages of development and lactation. J Endocrinol 155:501–511
Rabinowitz D, Laird N (2000) A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Hum Hered 50:211–223
Remy JJ, Lahbib-Mansais Y, Yerle M, Bozon V, Couture L, et al. (1995) The porcine follitropin receptor – cDNA cloning, functional expression and chromosomal localization of the gene. Gene 163:257–261
Rodriguez C, Tomas A, Alves E, Ramirez O, Arque M, et al. (2005) QTL mapping for teat number in an Iberian-by-Meishan pig intercross. Anim Genet 36:490–496
Rohrer GA (2000) Identification of quantitative trait loci affecting birth characters and accumulation of backfat and weight in a Meishan-White Composite resource population. J Anim Sci 78:2547–2553
Rohrer GA, Ford JJ, Wise TH, Vallet JL, Christenson RK (1999) Identification of quantitative trait loci affecting female reproductive traits in a multigeneration Meishan–White composite swine population. J Anim Sci 77:1385–1391
Schaapveld RQJ, Schepens HTG, Robinson GW, Attema J, Oerlemans F, et al. (1997) Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity. Dev Biol 188:134–146
Short TH, Rothschild MF, Southwood OI, McLaren DG, deVries A, et al. (1997) Effect of the estrogen receptor locus on reproduction and production traits in four commercial pig lines. J Anim Sci 75:3138–3142
Strange KS, Wilkinson D, Emerman JT (2002) Mitogenic properties of insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and epidermal growth factor on human breast epithelial cells in primary culture. Breast Cancer Res Treat 75:203–212
Strange KS, Wilkinson D, Edin G, Emerman JT (2004) Mitogenic properties of insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and epidermal growth factor on human breast stromal cells in primary culture. Breast Cancer Res Treat 84:77–84
Steffens S (1993) Stülpzitzen – ein Problem in der Schweinezucht. SUS Schweinezucht und Schweinemast 3:8–11
Tapanainen JS, Aittomaki K, Huhtaniemi IT (1997) New insights into the role of follicle-stimulating hormone in reproduction. Ann Med 29:265–266
Trakooljul N (2004) Molecular and association analyses of the androgen receptor gene as a candidate for production and reproduction traits in pigs. Thesis, Rheinische Friedrich-Wilhelms–Universität, Bonn
Visvader JE, Venter D, Hahm K, Santamaria M, Sum EYM, et al. (2001) The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proc Natl Acad Sci U S A 98:14452–14457
Vonderhaar BK, Greco AE (1979) Lobulo-alveolar development of mouse mammary-glands is regulated by thyroid-hormones. Endocrinology 104:409–418
Wada Y, Akita T, Awata T, Furukawa T, Sugai N, et al. (2000) Quantitative trait loci (QTL) analysis in a Meishan × Gottingen cross population. Anim Genet 31:376–384
Wimmers K, Chomdej S, Schellander K, Ponsuksili S (2002) Linkage mapping of SNPs in the porcine relaxin gene. Anim Genet 34:323–324
Wimmers K, Fiedler I, Hardge T, Murani E, Schellander K, et al. (2006) QTL for microstructural and biophysical muscle properties and body composition in pigs. BMC Genet 7:15
Wysolmerski JJ, Broadus AE, Zhou J, Fuchs E, Milstone LM, et al. (1994) Overexpression of parathyroid hormone-related protein in the skin of transgenic mice interferes with hair follicle development. Proc Acad Natl Sci U S A 91:1133–1137
Wysolmerski JJ, McCaugherncarucci JF, Daifotis AG, Broadus AE, Philbrick WM (1995) Overexpression of parathyroid hormone-related protein or parathyroid-hormone in transgenic mice impairs branching morphogenesis during mammary-gland development. Development 121:3539–3547
Yaswen P, Smoll A, Hosoda J, Parry G, Stampfer MR (1992) Protein product of a human intronless calmodulin-like gene shows tissue-specific expression and reduced abundance in transformed cells. Cell Growth Differ 3:335–345
Yue GH, Beeckmann P, Moser G, Muller E, Bartenschlager H, et al. (2003) QTL alleles on chromosome 7 from fatty Meishan pigs reduce fat deposition. Sci China C Life Sci 46:10–17
ZDS (Zentral Verband der Deutschen Schweineproduktion e. V) (2003) Richtlinie fuer die Stationspruefung auf Mastleistung, Schlachtkoerperwert und Fleischbeschaffenheit beim Schwein, 10 December 2003, Bonn, Germany
Zhao L, Roche PJ, Gunnersen JM, Hammond VE, Tregear GW, et al. (1999) Mice without a functional relaxin gene are unable to deliver milk to their pups. Endocrinology 140:445–453
Acknowledgments
This work was supported by funds provided by the Development Association for Biotechnology Research (FBF) and the Research Federal Ministry of Education and Research (BMBF).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jonas, E., Schreinemachers, HJ., Kleinwächter, T. et al. QTL for the heritable inverted teat defect in pigs. Mamm Genome 19, 127–138 (2008). https://doi.org/10.1007/s00335-007-9086-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-007-9086-5